Expression and Secretion of RANTES (CCL5) in Human Adipocytes in Response to Immunological Stimuli and Hypoxia

Obesity and related disorders represent states of systemic low-grade inflammation. Chemokine secretion by adipocytes may initiate leukocyte infiltration in obese adipose tissue and thus mediate an important step in the establishment of chronic immune activation. The chemokine RANTES (regulated upon activation normal T cell expressed and secreted)/CCL5 is a chemoattractant for various leukocyte subsets. This study was designed to examine whether RANTES is expressed and released by human adipocytes and how its expression is regulated. RANTES expression under basal conditions was studied in mature adipocytes. Cells were therefore challenged with lipopolysaccharide (LIPS), interferon (IFN)-gamma, interleukin (IL)-4, monocyte chemoattractant protein (MCP)-1 or exposed to low oxygen pressure. RANTES was expressed and secreted constitutively in most samples of mature adipocytes from the omental and the subcutaneous depot. RANTES release was dependent on adipocyte size and also seemed to be higher from cells of obese donors. Hypoxia (4%O-2) caused an approximately 36% increase of RANTES release. Human adipocytes express the chemokine RANTES and are thus identified as a novel cellular source of this immune mediator. LIPS and IFN gamma do not seem to play a significant role for the expression of RANTES in contrast to moderate hypoxia, which points to a distinct role in the innate immune system.